Reactivity | HuSpecies Glossary |
Applications | Bioactivity |
Format | Carrier-Free |
Details of Functionality | Measured by its ability to induce TNF-alpha secretion by JAWSII mouse immature dendritic cells. The ED50 for this effect is 1-4 µg/mL. |
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Source | Mouse myeloma cell line, NS0-derived human LAG-3 protein
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Accession # | |||||||
N-terminal Sequence | Leu23 |
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Structure / Form | Disulfide-linked homodimer |
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Protein/Peptide Type | Recombinant Proteins |
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Gene | LAG3 |
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Purity | >95%, by SDS-PAGE under reducing conditions and visualized by silver stain. |
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Endotoxin Note | <0.10 EU per 1 μg of the protein by the LAL method. |
Dilutions |
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Theoretical MW | 72.7 kDa (monomer). Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. |
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SDS-PAGE | 75-90 kDa, under reducing conditions. |
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Publications |
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Storage | Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
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Buffer | Lyophilized from a 0.2 μm filtered solution in PBS. |
Purity | >95%, by SDS-PAGE under reducing conditions and visualized by silver stain. |
Reconstitution Instructions | Reconstitute at 100 μg/mL in sterile PBS. Reconstitute 30 minutes prior to use with minimal agitation. |
LAG-3 (Lymphocyte activation gene-3), designated CD223, is a 70 kDa type I transmembrane protein that is a member of the immunoglobulin superfamily (IgSF) (1, 2). LAG-3 shares approximately 20% amino acid sequence homology with CD4, but has similar structure and binds to MHC class II with higher affinity, providing negative regulation of T cell receptor signaling (1, 2). Human LAG-3 cDNA encodes 525 amino acids (aa) that include a 28 aa signal sequence, a 422 aa extracellular domain (ECD) with four Ig-like domains, a transmembrane region and a highly charged cytoplasmic region. Within the ECD, human LAG-3 shares 70%, 67%, 76%, and 73% aa sequence identity with mouse, rat, porcine, and bovine LAG-3, respectively. LAG-3 is expressed on activated CD4+ and CD8+ T cells, NK cells, and plasmacytoid dendritic cells (pDC), but not on resting T cells (1-3). LAG-3 on activated CD4+CD25+ Treg cells plays a role in their suppressive activity (4). LAG-3 limits the expansion of activated T cells and pDC in response to selected stimuli (3-5). A soluble 54 kDa form, sLAG-3, can be shed by metalloproteinases ADAM10 and TACE/ADAM17 (6, 7). While monomeric sLAG-3 itself may be inactive, shedding allows for normal T cell activation by removing negative regulation (7). Binding of a homodimerized sLAG-3/Ig fusion protein to MHC class II molecules induces maturation of immature DC, and secretion of cytokines such as IFN-gamma and TNF-alpha by type 1 cytotoxic CD8+ T cells and NK cells (8, 9). sLAG-3/Ig has been used as a potential adjuvant to stimulate a cytotoxic anti-cancer immune response (9, 10). In mice, deletion of LAG-3 and another negative regulator, PD-1, facilitates anti-cancer response but also blocks self-tolerance and increases susceptibility to autoimmune diseases (11, 12). In humans, antibody-mediated down‑regulation of LAG-3 and PD-1 allows more effective control of chronic malaria, while in NOD (non‑obese diabetic) mice, deletion of LAG-3 alone accelerates diabetes (12-14).
Tired T cells: Hypoxia Drives T cell Exhaustion in the Tumor Microenvironment By Hunter MartinezThe paradigm shifting view of the immune system being leveraged to target cancer has led to numerous therapeutic breakthroughs. One major cell group responsible for this revelation is a T cell. ... Read full blog post. |
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